title: Effects of chemopreventive citrus phytochemicals on human P-glycoprotein and multidrug resistance protein 1.
abstract: The effects of dietary chemopreventive citrus phytochemicals on the drug efflux transporters P-glycoprotein (ABCB1) and multidrug resistance protein 1 (MRP1, ABCC1) were investigated using P-glycoprotein-overexpressing human carcinoma KB-C2 cells and human MRP1 gene-transfected KB/MRP cells. The effects of natural chemopreventive citrus phytochemicals, such as auraptene, nobiletin, citral, citronellal, limonene, limonin, and synephrine were examined. The accumulation of daunorubicin, a fluorescent substrate of P-glycoprotein, increased in the presence of auraptene and nobiletin in KB-C2 cells. Nobiletin also increased the accumulation of calcein, a fluorescent substrate of MRP1, in KB/MRP cells. The ATPase activity of P-glycoprotein was stimulated by auraptene and nobiletin. The ATPase activity of MRP1 was stimulated by nobiletin. These results suggest that chemopreventive citrus phytochemicals, such as nobiletin found in oranges, have inhibitory effects on P-glycoprotein and/or MRP1, and may cause food-drug interactions.
authors.affiliation: Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Japan. nabe@nupals.ac.jp
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nabekura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamaki
authors.forename: Shuji
authors.initials: S
authors.lastname: Kitagawa
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000187:drug effects* / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000378:metabolism; D002957:Citrus / Q000737:chemistry*; D003630:Daunorubicin / Q000378:metabolism; D005452:Fluoresceins / Q000378:metabolism; D018565:Food-Drug Interactions; D006801:Humans; D007624:KB Cells
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D005452:Fluoresceins; D000251:Adenosine Triphosphatases; C007740:fluorexon; D003630:Daunorubicin